Some 1-(4-aryl-2-thiazolyl)-3-(2-thienyl)-5-aryl-2-pyrazoline derivatives ( TP 1–28 ) were synthesized by reacting substituted 3-(2-thienyl)-5-aryl-1-thiocarbamoyl-2-pyrazolines ( P 1–7 ) with phenacyl bromides in ethanol. Structures of the synthesized compounds were confirmed by elemental analyses and IR, 1 H-NMR and MS-FAB+ spectral data. Their antimicrobial activities against Escherichia coli (NRRL B-3704), Staphylococcus aureus (NRLL B-767), Salmonella typhimurium (NRRL B-4420), Bacillus cereus (NRRL B-3711), Listeria monocytogenes (Ankara University, Faculty of Veterinary, Ankara, Turkey), Aeromonas hydrophila (Ankara University, Faculty of Veterinary, Ankara, Turkey), Candida albicans, and Candida glabrata (isolates obtained from Osmangazi University, Faculty of Medicine, Eskisehir Turkey) were investigated. A significant level of activity was illustrated.
The increasing clinical importance of drug-resistant fungal pathogens has urged additional need to fungal research and new antifungal compound development. For this purpose, some N-(1-benzyl-2-phenylethylidene)-N'-[4-(aryl)thiazol-2-yl]hydrazone (1a-e) and N-(1-phenylbutylidene)-N'-[4-(aryl)thiazol-2-yl]hydrazone (2a-e) derivatives were synthesised and evaluated for antifungal activity. Their antifungal activities against standard and clinical strands of Candida albicans, Candida glabrata, Candida utilis, Candida tropicalis, Candida krusei, Candida zeylanoides, and Candida parapsilosis were investigated. A significant level of activity was observed.
Some 2-(benzo[d]oxazol/benzo[d]imidazol-2-ylthio)-N-(9H-fluoren-9-yl)acetamide derivatives were synthesized by reacting 9-(chloroacetylamino)fluorene with benzo[d]oxazol/benzo[d]imidazol-2-thiole in acetone in the presence of K2CO3. Chemical structures of the compounds were elucidated by 1H NMR spectroscopy and FAB+ mass spectrometry. Their antimicrobial activities against Micrococcus luteus (NRLL B-4375), Bacillus cereus (NRRL B-3711), Proteus vulgaris (NRRL B-123), Salmonella typhimurium (NRRL B-4420), Staphylococcus aureus (NRRL B-767), Escherichia coli (NRRL B-3704), Candida albicans, and Candida glabrata were investigated, and significant activity was observed.
In this study, 14 different 2-[(1-methyl-1H-tetrazole-5-yl)thio]-1-(phenyl)ethanone derivatives (1–14) were synthesized. The structures of the obtained compounds were elucidated using IR, 1H-NMR, 13C-NMR and FAB+-MS spectral data and elemental analyses results. The compounds were screened for their anticandidal activity using the microbroth dilution method and for their cytotoxic effects using the MTT assay against NIH/3T3 cells. Some of the compounds were found to be potent anticandidal agents with weak cytotoxicities.
Targeted therapies have come into prominence in the ongoing battle against non-small cell lung cancer (NSCLC) because of the shortcomings of traditional chemotherapy. In this context, indole-based small molecules, which were synthesized efficiently, were subjected to an in vitro colorimetric assay to evaluate their cyclooxygenase (COX) inhibitory profiles. Compounds 3b and 4a were found to be the most selective COX-1 inhibitors in this series with IC50 values of 8.90 µM and 10.00 µM, respectively. In vitro and in vivo assays were performed to evaluate their anti-NSCLC and anti-inflammatory action, respectively. 2-(1H-Indol-3-yl)-N′-(4-morpholinobenzylidene)acetohydrazide (3b) showed selective cytotoxic activity against A549 human lung adenocarcinoma cells through apoptosis induction and Akt inhibition. The in vivo experimental data revealed that compound 3b decreased the serum myeloperoxidase and nitric oxide levels, pointing out its anti-inflammatory action. Moreover, compound 3b diminished the serum aminotransferase (particularly aspartate aminotransferase) levels. Based on the in vitro and in vivo experimental data, compound 3b stands out as a lead anti-NSCLC agent endowed with in vivo anti-inflammatory action, acting as a dual COX-1 and Akt inhibitor.
Background: Due to the increasing number of cases of invasive fungal infections (IFIs), there is an urgent need to identify potent antifungal agents capable of combating IFIs. Pyrazolines are one such class of therapeutically active agents that could be considered to fulfill this need. Objective: In this context, this paper aims to identify two new series of bis-pyrazolines endowed with potent antifungal activity against Candida albicans and Aspergillus niger. Methods: Two new series of bis-pyrazolines (4a-i, 5a-e) were synthesized through an efficient and versatile synthetic procedure. The compounds were screened for their antifungal effects on C. albicans and A. niger using a broth microdilution method. Their cytotoxic effects on NIH/3T3 mouse embryonic fibroblast cells were determined using MTT assay. Molecular docking studies were performed in the active site of lanosterol 14α-demethylase (CYP51) to shed light on their antifungal effects using Schrödinger’s Maestro molecular modeling package. Results: 5,5'-(1,4-Phenylene)bis[1-(2-(5-phenyl-1,3,4-oxadiazol-2-yl)thio)acetyl)-3-(2-thienyl)-4,5- dihydro-1H-pyrazole] (4a) and 5,5'-(1,4-phenylene)bis[1-(2-(4-(2-hydroxyethyl)-1-piperazinylthiocarbamoyl) thio)acetyl)-3-(2-thienyl)-4,5-dihydro-1H-pyrazole] (5a) were found as the most promising antifungal agents in this series. Compounds 4a and 5a showed pronounced antifungal activity against C. albicans (MIC= 0.016 mg/mL) and A. niger (MIC= 0.008 mg/mL). Based on MTT assay, their antifungal effects were selective (IC 50 > 0.500 mg/mL for NIH/3T3 cell line). Molecular docking studies suggested that compounds 5a-e might show their anticandidal effects via CYP51 inhibition in regard to their stronger interactions in the active site of CYP51. Conclusion: Compounds 4a and 5a stand out as potential antifungal agents for the management of IFIs caused by C. albicans and A. niger.
Abstract 1‐( p ‐Methylphenyl)‐3,5‐diaryl‐2‐pyrazoline derivatives ( 2a–f ) were synthesized via the treatment of 1‐(1 H ‐indol‐3‐yl)‐3‐aryl‐2‐propen‐1‐ones ( 1a–f ) with p ‐methylphenylhydrazine hydrochloride in hot acetic acid. The structures of these compounds were elucidated by IR, 1 H NMR, and mass spectral data and elemental analysis. These compounds were investigated for their antimicrobial activity. Brine‐Shrimp lethality assay was carried out to determine the toxicity of the compounds. Compound 2e , which is the pyrazoline derivative bearing the 2,5‐dichlorophenyl moiety, can be identified as the most promising agent against Klebsiella pneumoniae (ATCC 13883) and Candida glabrata (ATCC 36583) due to its inhibitory effects on K. pneumoniae and C. glabrata with a MIC value of 100 µg/mL as a non‐toxic agent (LC 50 > 1000 µg/mL).
